4-95052055-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001203.3(BMPR1B):c.-17-52353A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,314 control chromosomes in the GnomAD database, including 511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.057 (511 hom., cov: 32)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.909

Genes affected

BMPR1B (HGNC:1077): (bone morphogenetic protein receptor type 1B) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 4-95052055-A-T is Benign according to our data. Variant chr4-95052055-A-T is described in ClinVar as [Benign]. Clinvar id is 1175514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1B	NM_001203.3	c.-17-52353A>T		intron_variant		ENST00000515059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-17-52353A>T		intron_variant		1	NM_001203.3	P4

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8637 AN: 152196 Hom.: 511 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0568 AC: 8653 AN: 152314 Hom.: 511 Cov.: 32 AF XY: 0.0548 AC XY: 4081 AN XY: 74478

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0400 Hom.: 27

Bravo AF: 0.0615

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.3
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59779792; hg19: chr4-95973206;